In 60 patients diagnosed by defined criteria as having disabling or severe headache and in whom a variety of clinical variables will be recorded, a comparative trial of amitriptyline (A), propranolol (PR) and placebo (PL) as prophylaxes will be monitored over a period of up to 44 weeks. Patients still keep daily records of quantitated severity and duration of headache from which a headache score will be calculated. The clinical experiment will be of a double-blind crossover. Crossover design medication will be dispensed in identical-appearing capsules, patients to take 3 capsules daily with the pharmacist the only member of the team with the code, dispensing medication. After elimination of placebo responders, patients will be seen at 4-week intervals and placed on A, PR or PL in a randomized sequence. For each active drug there will be a week of rising dosage at the beginning and a week of tapering dosage at the end of that treatment period. Change in dosage during the treatment module will be determined from defined criteria utilizing toxicity data supplied by the physician, and headache relief or lack of same noted on a patient calendar. A computer will, from these data, calculate the proper dosage change. Serum levels of PR and A will be determined at 4-week intervals during each patient's period on each drug. Several psychological parameters will be measured at the beginning of the experiment, and some will be retested at each patient visit. Appropriate tests for pharmacological actions of A and PR will be done. Analgesic ingestion will be measured. The variation in platelet uptake of serotonin and in platelet serotonin release will be measured at the beginning of the study and at each patient visit. By appropriate statistical methods the following will be studied: (1) the overall comparative efficacy of PR and A in prophylaxis of migraine, (2) the clinical and psychological variables associated with therapeutic effect for each drug, (3) the association of drug serum levels with therapeutic and toxic effect, with analgesic use, and with clinical pharmacological effects, and (4) the study of patient compliance using patient self-reporting and drug serum levels.